This study will examine the relation of prenatal influenza and pro-inflammatory cytokines to the risk of schizophrenia and other schizophrenia spectrum disorders (SSD), using serologic methods to document the exposures of interest. The proposed study builds upon a unique investigation, the Prenatal Determinants of Schizophrenia (PDS) Study, a follow-up of SSD in a large birth cohort. This study has many strengths, including a large and representative sample of births, and a rich array of prospectively collected data on developmental antecedents. In the present proposal, we seek to capitalize on an additional and unique resource of this birth cohort--archived maternal serum specimens that were drawn during the pregnancies of cohort members. These samples have been stored frozen since the time that they were acquired, and are available for analysis. This resource will permit us to examine for the first time serologically documented prenatal infection, a plausible risk factor for SSD. Specifically, we shall: 1) Examine the relation between serologically documented prenatal influenza infection during mid-gestation and risk of SSD. We hypothesize that there will be a higher rate of seroconversion to influenza in prenatal sera of SSD cases as compared to matched controls. For this purpose, we shall document seroconversion for influenza antibody in prenatal sera of 100 SSD cases and 400 matched controls from the PDS birth cohort, compare the proportions with seroconversion for influenza between the two groups, and compute odds ratios with confidence intervals using methods appropriate for matched data; 2) Examine the relation between serologically documented maternal pro-inflammatory cytokines in the etiology of SSD. This will represent an important first step toward investigating other prenatal infections in the etiology of SSD. We hypothesize that there will be increased levels of four specific cytokines-- interleukin 1-beta (IL-1-beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF- alpha)--during mid-gestation among mothers of SSD, as compared to control, offspring. For this purpose, we shall quantify levels of these cytokines in 100 SSD cases and their respective matched controls, and compare these levels between the groups.